Ethosuximide increases lifespan and improves sensorimotor function in C. elegans ANCL and frontotemporal dementia models.
a Ethosuximide extends lifespan in dnj-14 mutants. Viability of age-synchronised dnj-14(ok237) animals grown in the presence of the indicated concentrations of ethosuximide was determined; untreated wild type control N2 worms are shown for comparison (n = 50-55 worms for each concentration). b Ethosuximide ameliorates the dnj-14 food sensing defect. The time taken to move to a bacterial food source was measured in wild type N2 and dnj-14(tm3223) strains grown until 5-6 days of age in the presence or absence of ethosuximide (n = 71-80 worms of each strain per condition). c Ethosuximide increases locomotion in Tau V337M worms, but not control worms. Thrashing in solution was measured in Tau V337M worms grown until 1 and 3 days of age and assayed in the presence of the indicated concentrations of ethosuximide (for each age group, n = 120-140 worms for 0 mg/l; n = 38-40 worms for 0.1, 0.2 and 0.5 mg/ml; n = 80-90 worms for 1 and 2 mg/ml;). Identically treated wild type control CZ1200 worms are shown for comparison (n = 20 worms per concentration). Data are shown as mean ± SEM (***p < 0.001). d Age-dependence of ethosuximide’s effect on Tau V337M locomotion. Thrashing assays were performed on age-synchronised animals grown in the presence or absence of 2 mg/ml ethosuximide (n = 30-50 worms per data point). Data are shown as mean ± SEM (***p < 0.001, *p < 0.05). e Ethosuximide increases lifespan in Tau V337M worms. Viability of age-synchronised animals grown in the presence of the indicated concentrations of ethosuximide was determined in comparison to untreated wild type control CZ1200 worms (n = 50-102 worms for each drug concentration). f Comparison of the ethosuximide concentration-dependence of mean lifespan extension in dnj-14 and Tau V337M worms